Keywords

1 Introduction

Plants play a vital role in our diet and are an excellent reservoir of proteins, carbohydrates, antioxidants, vitamins, and other important components required for our existence (Vella 1990). Among such important components, secondary metabolites have received increasing attention, as they contain medicinal values with huge therapeutic significance, besides being major contributors to health care improvements (Eloff 1998). Such secondary metabolites are often named active compounds or phytochemicals and display renowned biological effects, such as antimicrobial, antioxidant, antitumor, antidiabetic, antinociceptive, cardioprotective, and immunomodulatory properties, among others. Indeed, the increasing importance on the use of herbal preparations and medicinal plant is that they have low or even no side effects when compared to synthetic drugs and are simultaneously more potent against several diseases and disorders.

From time immemorial, a variety of indigenous and cultivated plants have been exploited for their therapeutic properties, and globally they are analyzed for the assessment of their efficiency as a result of increasing demand by the worldwide population by plant-based medicine. The World Health Organization (WHO) has reported that the business of medicinal plants and herbal medicine and the demand for herbal raw material is increasing annually at a growth rate of almost 15% (Neupane and Lamichhane 2020). However, it is expected that the global market of medicinal or pharmaceutical products extracted from plant sources will surpass $111 billion by the year 2023 (Sofowora et al. 2013; Neupane and Lamichhane 2020). Hence, the research for identifying new species of medicinally important plants and the search for biologically active compounds from them is in progressing phase, due to which the demand for these medicinal plants has increased a lot in the market.

The forest richness of the Himalayan region is inexhaustible with exceptional medicinal flora and incredible economic significance (Pandey 2007). Flora from the Himalayan region is used by native communities for different reasons, including food, fuel, and medicinal purposes (Detwiler and Hall 1988; Bhat et al. 2020). A huge range of Himalayan plants has been cited by researchers around the world, with multiple therapeutic virtues underlined as well as their major role in traditional medicinal systems of different countries.

Currently, numerous herbal medicines and their active components have been used directly or indirectly in the modern medical system. A plethora of biologically important active compounds has been isolated from plant species found in the Himalayan region. Among such active compounds, linoleic acid, quercetin, gallic acid, ascorbic acid, piperine, myricetin, curcumin, taxol, palmitic acid, cinnamaldehyde, nerolidol, taxiresinols, amarogentin, swertiamarin, mangiferin, hesperidin, picroliv, and apocynin have been extracted and/or isolated at considerable amounts from a variety of plants, including Anogeissus latifolia, Justicia adhatoda, Curcuma longa, Punica granatum, Piper nigrum, Aegle marmelos, Rhododendron arboreum, R. campanulatum, Podophyllum hexandrum, Saussurea obvallata, Taxus wallichiana, Pinus roxburghii, Swertia chirayita, Picrorhiza kurroa, etc., to whom excellent therapeutic activities have been attributed, such as antimicrobial, anticancer, anti-inflammatory, antiproliferative, antioxidant, antiatherogenic, anti-asthmatic, antifungal, antidiabetic, immunomodulatory, anti-HIV, anti-Parkinson, and anti-hepatitis effects (Rajeshkumar and Kuttan 2001; Juyal et al. 2014; Painuli et al. 2015; Kumar and Van Staden 2016; Painuli and Kumar 2016; Painuli et al. 2016; Semwal 2017; Adnan et al. 2019; Semwal and Painuli 2019; Soni and Grover 2019). In this sense, this chapter aims to address the important medicinal plants from the forests of the Himalayas and their traditional uses, promising bioactive molecules along with therapeutic potential.

2 From Himalayan Mountain Diversity to New Drug Sources

The Himalaya, a crescent-shaped continuous belt of mountain system located in Asia, is known to be the highest and youngest mountain range worldwide. It extends over about 2500 km from Nanga Parbat in the west to Namja Barwa in the east, ranging up to 350 km of width in the west to 150 km in the east. This mountain belt is mainly distributed across the territories of five countries, namely, Pakistan, India, Nepal, China, and Bhutan (Roy and Purohit 2018). From west to east, the Himalayan belt is sectioned into three well-defined regions: western, eastern, and central Himalayan. With a complex and diverse geological pattern in terms of hydrology, environment, erosion, and mass movement, in the Himalayan belt, there is a marked climate variation at different zones, drifting from the tropical climate at the bottom and everlasting snow at the top of the mountain, with regional ecosystem transformations depending on elevation. In fact, both altitudinal and climatic variations make the Himalayan vegetation extremely rich and broadly distributed in forests and grasslands (Hajra and Rao 1990). Himalaya forest systems vary markedly in their topography, soils, rainfall, and weather, harboring rare and valuable flora and fauna. The variation in Himalayan vegetation ranges from tropical deciduous forests at the lower altitude to temperate forest at middle altitude, while at higher altitudes, coniferous forest, subalpine, and alpine forests are found, ranging from alpine grasslands and meadows to scrublands and permanent snowline.

Among the wide plant biodiversity of the Himalayan forest, which includes medicinal, aromatic, and wild edible plants, orchids, ferns and fern allies, bamboos, and ornamental plants (Hajra and Rao 1990), with increasing elevation, the flora shows even greater diversity profile (Manish and Pandit 2018; Bhat et al. 2020). The major plant species in the Himalayan tropical and subtropical forests include Acacia catechu, A. procera, Albizia lebbeck, Bombax ceiba, Careya arborea, Dalbergia sissoo, Duabanga grandiflora, Garuga pinnata, Gmelina arborea, Haldina cordifolia, Kydia calycina, Mesua assamica, M. ferrea, Oroxylum indicum, Pinus roxburghii, Quercus lamellose, Semecarpus anacardium, Shorea robusta, Terminalia tomentosa, and T. bellirica; however, in the Himalayan temperate forest, species like Abies delavayi, A. densa, A. pindrow, Acer spp., Berberis spp., Cedrus deodara, Larix griffithii, Lithocarpus pachyphyllus, Magnolia spp., Picea smithiana, Prinsepia utilis, Quercus cerris, Q. lamellose, Rhododendron spp., and Tsuga dumosa predominate (Manish and Pandit 2018). In the shrubby region, Artemisia, Berberis, Cotoneaster, and Ephedra species are major elements, while in subalpine and alpine zones, Aconitum heterophyllum, Aster albescens, Anemone, Berberis, Cotoneaster, Geranium, Iris, Juniperus, Lloydia, Potentilla, Primula, and Rhododendron dominate (Srivastava et al. 2017; Manish and Pandit 2018). Table 1 enumerates the list of some Himalayan plants along with their distribution.

Table 1 Some popular Himalayan plants and their distribution
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3 Traditional Uses of Himalayan Plants

The traditional system of medicine (TSM) comprises folk knowledge-based medicines, exercises, manual techniques, and spiritual healing along with other medical aspects developed over generations by several communities for diagnosis and prevention of a plethora of diseases. According to the WHO, “the traditional medicine is the sum total of the knowledge, skills, and practices based on theories, beliefs and experiences indigenous to different cultures, whether explicable or not, used in health maintenance as well as prevention, diagnosis, improvement or even treatment of physical and mental illness” (Che et al. 2017). TSM uses natural compounds, extracted from herbs, animals, organic matter, and minerals, for preventing or curing diseases, with medicinal plants being used for preparing a plethora of herbal drug formulations. TSM, including Ayurveda, Yoga, Unani, Naturopathy, Siddha, Homeopathy, and Chinese medicine system (TCM) used Himalayan medicinal plants as a leading source for efficient and effective herbal drug formulation. Among all, the Ayurvedic medicinal system is the oldest system of medicine developed and is in practice since 1500 BC (Ravishankar and Shukla 2007). These different TSMs are practiced in India, Nepal, Srilanka, Pakistan, Bangladesh, Bhutan, China, and Tibet, among other places (Rosenberg 2012; Samal and Dehury 2016).

Among the renowned plant species that play important roles in these TSM , Andrographis paniculate, Artemisia maritime, Asparagus racemosus, Bacopa monnier, Barbarea vulgaris, Berberis vulgaris, Cedrus deodara, Curcuma longa, Datura innoxia, Dioscorea deltoidea, Equisetum arvense, Girardinia heterophylla, Ocimum sanctum, Paeonia emodi, Picrorrhiza kurroa, Pinus gerardiana, Podophyllum hexandrum, Rheum emodi, Rhododendron arboreum, Saussurea obvallata, Terminalia chebula, Tulipa gesneriana, and Withania somnifera are the most widely recognized (Kurup 2002; Khare 2008; Gautam and Bhadauria 2009). These herbal plants exhibit numerous biological properties and have been used to treat high blood pressure, migraine, parasitic and fungal infections, fever, skin problems, cancer, stomach ache, uterine infection, inflammation, microbial infection, stress, fatigue, liver, and kidney problems (Joshi and Joshi 2013; Chaudhury and Rafei 2002). Some of these traditionally important plants and their traditional uses are mentioned in Table 2.

Table 2 Some popular medicinal plants and their traditional uses
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On the other hand, the TCM system was written around 100 or 200 BC, and the Chinese Materia Medica was published in 1977 (Yuan et al. 2016). Regarding the most frequently used Himalayan medicinal plants in TCM, Aquilaria sinensis, Bergeria purpurascens, Cistanche salsa, Coptis omeiensis, Coptis teeta, Cordyceps sinensis, Dendrobium spp., Dioscorea deltoidea, Dioscorea ipponica, Dioscorea zingiberensis, Dracaena cochinchinensis, Ephedra sinica, Epimedium brevicornum, Erigeron breviscapus, Eucommia ulmoides, Fritillaria spp., Gastrodia alata, Gentiana macrophylla, Gentiana scabra, Glycyrrhiza uralensis, Homalomena occulta, Panax ginseng, Panax pseudoginseng, Paris polyphylla var. yunnanensis, Picrorhiza scorophulariiflora, Psammosilene tunicoides, Rauwolfia yunnanensis, Rheum officinale, Salvia miltiorrhiza, Saussurea lappa, Sinopodophyllum emodi, Stephania epigaea, Stephania yunnanensis, Taxus chinensis, and Taxus wallichiana are the most evident (Shengji et al. 2009). Indeed, the Himalayan flora has a long history in traditional or alternative treatments , and presently researchers are not only searching for new active components but also exploring the mechanism of action of many of these plant-derived extracts and even single components.

4 Plant-derived Bioactive Compounds

Bioactive compounds are essential and nonessential elements extracted from natural sources, especially from plants that help fulfill vital health requirements. Secondary metabolism produces these specialized compounds as a self-defense mechanism, conferring protection against herbivores, insects, pathogen, pests, pathogens, and harsh environmental conditions (Egbuna et al. 2018). These secondary metabolites, also known as phytochemicals, phytoconstituents, or even active compounds, have microbicidal, insecticidal, and pesticidal effects and are also of huge interest for the production of several pharmaceutical drugs. Moreover, they also have numerous biomedicinal properties , such as antioxidant, anti-inflammatory, cardiovascular, anti-allergic, antihypertensive, and anticancer potentialities, being, therefore, a rich source of nutraceutical and pharmaceutical products (Hussein and El-Anssary 2018).

The Himalayan flora are known worldwide for their wide spectrum of biological activities , attributed to the presence of high-valued secondary metabolites (Semwal et al. 2020). The plant species at higher altitudes have high diversity and a significant amount of several phytoconstituents, as they face high radiations, low soil nutrients, moisture stress, harsh temperature, and other adverse environmental conditions (Pandey et al. 2018; Yang et al. 2018). At higher altitude, phytoconstituents also help in pollination and confer protection and defense against several biotic and abiotic stresses (Demasi et al. 2018), with this plant–environmental interconnection being responsible for the unique mixture and composition of active compounds (Yang et al. 2018; Jurić et al. 2020).

Despite being put in the background for several years, today, there has been a growing interest in plant secondary metabolites over synthetic molecules because of several properties, such as low or no side effects, less toxicity, cost-effectiveness, and easy availability (Zeb et al. 2014). Many studies have suggested that natural compounds that are directly or indirectly isolated from plant origin actively participates in the formulation of effective and potent drugs. Currently, the field of synthetic chemistry is well developed yet, with more than 850 plant-derived active molecules being used in pharmaceutical formulations and with more than 100 plant-based compounds/molecules in the phase of clinical trials (Fowler 2006; Katiyar et al. 2012). Aspirin, ephedrine, colchicine, taxol, digoxin, camptothecin, atropine, and artemisinin are some of the plant-based active phytochemicals used in modern medicine (Jan and Abbas 2018; Calixto 2019).

Secondary metabolites are majorly classified into four main groups, such as alkaloids, terpenes, terpenoids, and polyphenolic compounds. Glycosides, tannins, and saponins are part of them, given their specific structure. Alkaloids are well-studied plant metabolites with remarkable anticancer, antimalarial, antihypertensive, anti-asthmatic, antimicrobial, analgesic, and vasodilatory activities (Roberts and Wink 1998; Raymond et al. 2010; Cushnie et al. 2014). Terpenes and terpenoids are major constituents of plant essential oil and exhibit great anti-inflammatory, anticancer, and antimicrobial activities (Trombetta et al. 2005; Salminen et al. 2008). Polyphenols are a vast group of phytochemicals, which include flavonoids, phenolic acids, isoflavonoids, lignans, curcuminoids, and tannins, possessing immense biomedicinal potentialities like anticancer, antimicrobial, anti-inflammatory, antioxidant, antidiabetic, neuroprotective, and antiallergic effects, among others (Huang et al. 2010; Ghasemzadeh and Ghasemzadeh 2011; Ferrazzano et al. 2011; Egbuna et al. 2018).

4.1 Alkaloids

Alkaloids are a group of naturally occurring organic compounds obtained from bacteria, plants, and fungi that contain at least one nitrogen atom in their heterocyclic ring (Mueller-Harvey and McAllan 1992). Ancient records have shown that alkaloids have been used for medicinal purposes since 4000 BC and are probably the first natural compounds (e.g., morphine) extracted from plants (Rao et al. 1978; Roberts and Wink 1998). Indeed, the therapeutic use of poppy and opium by Persians, Egyptians, Arabs, Greeks, and Sumerians has been mentioned in various ancient manuscripts.

Although they are known for their exceptional biomedicinal properties, several alkaloids with high toxic effects have been reported to cause death in minor amounts. For example, the evaluation of active compounds from Kopsia genus leads to the revelation of various classes of alkaloids, with antitumor, anti-leishmania, and antimitotic properties (Chen et al. 2012). Thus, based on their heterocyclic ring, alkaloids are classified as pyrrolidine alkaloids, pyridine alkaloids, pyrrolidine–pyridine alkaloids, pyridine–piperidine alkaloids, quinoline alkaloids, and isoquinoline alkaloids (Jan and Abbas 2018). These groups are comprised of medicinally important alkaloids, including hygrine, isopelletierine, piperine, coniine, nicotine, myosmine, quinine, taxol, hyoscyamine, scopolamine, papaverine, morphine, codeine, narcotine, and heroine (Saxena et al. 2013). Moreover, some alkaloids, including anabasine and nicotine, have insecticidal properties, while others like tetrahydropalmatine, isoquinoline, zephyrantine, berberine, palmatine, atropine, scopolamine, atropine, quinine, colchicine, ephedrine, hyoscyamine, morphine, taxol, emetine, and narcyclasine glucoside have a long history of medicinal applications and are pharmacologically important (Bribi 2018; Jan and Abbas 2018; Badri et al. 2019).

In general, various therapeutic activities have been reported to alkaloids, such as anticancer, antihyperglycemic, antimalarial, anti-asthmatic, vasodilatory, anti-arrhythmic, cholinomimetic, and analgesic effects (Roberts and Wink 1998; Sinatra et al. 2010; Russo et al. 2013; Kittakoop et al. 2014; Cushnie et al. 2014), with Himalayan plants, like Aconitum balfourii, Aconitum heterophyllum, Atropa belladonna, Berberis asiatica, Camellia sinensis, Cinchona officinalis, Colchicum luteum, Corydalis govaniana, Datura innoxia, Dicentra canadensis, Ephedra gerardiana, Eupatorium cannabinum, Rauvolfia serpentina , Saussurea lappa, Taxus baccata, Thalictrum foliolosum, Valeriana dubia, Vinca rosea, and Withania somnifera being extremely rich sources of such class of biologically active molecules (Khare 2008; Sharma and Gaur 2012; Chhetri 2014).

4.2 Terpenes and Terpenoids

Terpenes and terpenoids are one of the most common and diverse groups of plant secondary metabolites, with around more than 22,000 compounds occurring in all plant sorts (Adeyemi 2011). Briefly, terpenes are simple hydrocarbons consisting of five-carbon isoprene units, assembled in thousands of different ways. On the other hand, terpenoids are modified terpenes with different functional groups and oxidized methyl group present or absent at several locations (Tiwari and Rana 2015; Perveen and Al-Taweel 2018). They are the main constituents of essential oils (Joshi et al. 2016), namely, sesquiterpenes, saponins, iridoids, cardiotonic heterosides, alpha-terpineol, γ-terpinene, terpinolene, and terpinen-4-ol (Joshi et al. 2016). Organoleptically, terpenes, and terpenoids are responsible for the aroma and flavoring properties of plants, with compounds like linalool, caryophyllene, menthol, and geraniol being widely renowned for it. They also possess a broad range of pharmacological and biological properties, such as anti-inflammatory, antiparasitic, antioxidant, anticancer, antiviral, antimicrobial, insecticidal, and antihyperglycemic effects (Zhu et al. 2003; Trombetta et al. 2005; Salminen et al. 2008; Hanuš and Hod 2020). Himalayan flora , namely Abies pindrow¸ Achillea millefolium, Achyranthes bidentata¸ Aconitum chasmanthum, Aconitum ferox, Aconitum palmatum, Adiantum capillus-veneris, Andrographis panicultata, Artemisia maritima, Artemisia vestita, Baliospermum montanum, Blumea balsamifera, Bridelia montana, Bupleurum flacutum, Callicarpa macrophylla, Caltha palustris, Cedrus deodara, Cetraria islandica, Cimicifuga racemose, Curcuma angustifolia, Daphne oleoides, Delphinium denudatum, Euonymus tingens, Eupatorium cannabinum, Galium aparine, Inula racemose, Juniperus communis, Kalanchoe integra, Madhuca butyracea, Nardostachys jatamansi, Perilla frutescens Picea smithiana, Quercus incana, Rhododendron arboreum, Rhododendron campanulatum, Rhododendron cinnabarinum, Roylea cinereal, and Saussurea lappa, are well recognized for their rich contents in terpenes and terpenoids, with multiple applications in chemical, cosmetic, and pharmaceutical industries (Khare 2008; Painuli et al. 2015; Painuli et al. 2016; Rawat et al. 2019).

4.3 Phenolic Compounds

Polyphenols are widely known for their excellent antioxidant properties and ability to enhance the function of endogenous antioxidants, vitamins, and enzymes to prevent oxidative stress-induced damages by the high amount of reactive oxygen species (ROS). This group of biologically active molecules is considered to have chemical features related to phenolic substances and is composed of various subgroups, namely, phenolic acids, flavonoids, phytoalexins anthocyanins, lignin, tannins, and furanocoumarins (Tsao 2010; Singla et al. 2019). Synthesized by malonic and shikimic acid pathways occurring in plants, there are over 8,000 known structures of phenolics of which more than 4,000 are recognized as flavonoids (Bravo 1998; Harborne and Willians 2000; Cheynier 2005). Polyphenols possess a wide range of biological activities, including antioxidant, antiaging, anticancer, anti-inflammatory, anti-atherosclerotic, anti-apoptotic, cardioprotective, and neuroprotective abilities (Han et al. 2007; Soto-Hernández et al. 2017), with the major groups responsible for such effects being phenolic acids and flavonoids.

Himalayan flora is also a rich source of secondary metabolites and particularly has high contents of polyphenols. Many studies have proved that plant species from higher altitudes contain high and diverse polyphenolic forms. Among the Himalayan plants, Aegle marmelos, Ampelocissus latifolia, Artemisia sp., Berberis asiatica, Bergenia ciliate, Dendrobenthamia capitata, Fagopyrum esculentum, Ficus palmata, Ficus subincisa, Grewia optiva, Hippophae rhamnoides, Hypecoum leptocarpum, Hypericum perforatum, Leea asiatica, Meconopsis aculeata Royle, Morus alba, Morus serrata, Nardostachys jatamansi, Paris polyphylla, Pinus Species, Podophyllum hexandrum, Potentilla fulgens, Prunus cerasoides, Pyracantha crenulata, Reinwardtia indica, Rubus ellipticus, Satyrium nepalense, Saussurea obvallata, Taxus wallichiana, Viburnum mullaha, Vitis jacquemontii, Ziziphus mauritiana, Ziziphus nummularia, and Vaccinium glaucoalbum have been reported to have high polyphenolic content with rich biological activities (Prakash et al. 2007; Kaur et al. 2009; Ratan and Kothiyal 2011; Singh et al. 2015; Kundu et al. 2016; Feng et al. 2017; Mishra et al. 2018; Mohd et al. 2018; Painuli et al. 2018; Bahukhandi et al. 2019; Semwal and Painuli 2019; Singh et al. 2019; Rawat et al. 2019; Belwal et al. 2020; Gauchan et al. 2020; Tewari et al. 2020).

5 Biological Activities

At present, the earth’s population exceeds 7 billion and is continuously increasing at the rate of 1.05% per year, and as a consequence, humans have directly or indirectly influenced almost all parts of the planet (Vitousek et al. 1997; Lindahl and Grace 2015). The rise in anthropogenic activities not only influences the planet's environment but also triggers human health problems (Myers and Patz 2009). There are a number of factors, like food and water scarcity, climate change, globalization, urbanization, among others, that are a root cause of diseases and disorders in humans. According to the WHO Report in 2016, ischemic heart disease, stroke, respiratory infections, cancer, diabetes, and tuberculosis are some of the diseases with highest mortality rates. The factors responsible for such disorders can be intrinsic (e.g., genetic disorders, malfunctioning of the immune system, and hormonal imbalance) and extrinsic (e.g., radiations, harmful chemicals, bacteria, viruses, and fungi). Presently, in our day-to-day life, we are more exposed to these external factors, especially harmful radiations, chemicals, and mutated pathogens, like multidrug resistance bacteria and viruses, like severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS), due to which we suffer from deadly diseases.

The Himalayan region is one of the major habitats for medicinally important plant species for millennia. Dhar (2002) reported that the Himalayan region has a rich biodiversity, with around 21 vegetation types, 11 forest formations, and 10 forest types. The diverse climatic and geological conditions of the Himalayas are responsible for different types of flora and active compounds found in them, accountable for multiple medicinal properties. As previously referred, Himalayan plant species have remarkable antioxidant, anticancer, antimicrobial, antidiabetic, antiparasitic, analgesic, neuroprotective, antihepatotoxic, antihypertensive, anti-inflammatory, antiallergic, and anti-stress abilities (Khare 2008; Joshi et al. 2016). For example, Aconitum heterophyllum possesses antioxidant, anti-inflammatory, alexipharmic, antiflatulent, and analgesic effects, while the diterpenoid alkaloid isolated from the plant shows antioxidant and anticholinesterase properties (Ahmad et al. 2017; Paramanick et al. 2017). On the other hand, Arctium lappa is reported to possess anticancer, hepatoprotective, antidiabetic, anti-inflammatory, and antihuman immunodeficiency virus (HIV) properties (Chan et al. 2011; Gao et al. 2018). Atropa acuminata ethanol extract has revealed anti-arthritic effects, while the plant-derived phytoconstituents possess anticholinergic, antimicrobial, and anti-inflammatory activities and have wide medicinal uses in cardiology, gastroenterology, and ophthalmology (Rahman et al. 2018). Berberis aristata is reported to have antidiarrheal, hepatoprotective, antimicrobial, anticancer, antidiabetic, antiplatelet activating factor (paf), cardiotonic, and anti-inflammatory effects (Potdar et al., 2012). Dioscorea deltoidea is used for its prominent therapeutic effects in solving female reproductive system problems, central nervous system (CNS) and skin diseases, autoimmune diseases, oncology, cardiovascular system, bones and joint diseases, and metabolic disorders (Dangwal and Chauhan 2015). Hedychium spicatum holds anti-inflammatory, anti-asthmatic, anti-allergic, analgesic, antiulcer, hepatoprotective, antihyperglycemic, anticancer, and cytotoxic effects (Rawat et al. 2018). Nardostachys jatamansi is reported to possess antifungal, hepatoprotective, CNS, anticonvulsant, neuroprotective, anti-Parkinson’s, and antidiabetic activities (Purnima and Kothiyal 2015). Picrorhiza kurrooa has antioxidant, antimicrobial, hepatoprotective, antimutagenic, and anticancer activities (Masood et al. 2015). Podophyllotoxin is an active compound from P. hexandrum used in the synthesis of the anticancer drugs etoposide and teniposide (Giri and Narasu 2000). Rhododendron arboreum possesses antioxidant, adaptogenic, anti-inflammatory, antinociceptive, hepatoprotective, antidiabetic, cardioprotective, antimicrobial, and immunomodulatory activities (Popescu and Kopp 2013; Painuli et al. 2018). Swertia chirayita exhibits a broad range of bio-medicinal properties, like antiviral, antidiabetic, anti-inflammatory, anticancer, antioxidant, and antimicrobial effects (Kumar and Van Staden 2016). In addition, Artemisia, Cinnamomum, Cymbopogon, Junipers, Nepeta, Origanum, and Valeriana species are some other important plant genus from the Himalayan region with a wide range of polyphenols and with significant biomedicinal activities (Joshi et al. 2016). Different biological applications of the plants are presented in Fig. 1.

Fig. 1
figure 1

Different biological applications of the plants

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6 Pharmacological Effects of Himalayan Plant-derived Phytochemicals

6.1 Anticancer Activity

Cancer is considered the second major cause of mortality worldwide. Broadly, it not only affects the mental and physiological status of individuals but also has a huge social impact on the worldwide economy. Cancer therapy seems to be difficult, as most existing drugs and treatments are not very potent in conferring complete protection against the disease. The major steps involved in anticancer drug development are to assess both safety and efficacy in human models through clinical trials. Despite the huge amount of molecules with promising potential, from these studies, normally consisting of 4 phases (Phase I, II, III, and IV), unfortunately only one of every 5000–10,000 anticancer drugs get approval from the FDA, and only 5% of oncology drugs enter the phase I clinical trial (Paul et al. 2010; Petsko 2010; Shibue and Weinberg 2017; Bedard et al. 2020). Thus, the developmental cost of synthetic anticancer agents is extremely high; however, it can be reduced by introducing plant-based anticancer agents. Plant-derived active compounds have been detected to be effective in experimental and clinical trials against cancer. For example, the compound genistein (isoflavone) extracted from legumes and used for the treatment of various diseases including breast cancer, osteoporosis, obesity, and menopause reveals to be safe and effective at low cost (Zhang et al. 2020). In addition, Vincristine (Catharanthus roseus), Vinblastine (Catharanthus roseus), 5-Fluorouracil (Withania somnifera), Paclitaxel (Taxus brevifolia), Bullatacin (Annona squamosa), Theabrownin (Camellia sinensis), Solamargine (Solanum nigrum), Psoralidin (Psoralea corylifolia), Kaempferol galactoside (Bauhinia variegata), Skimmianine (Aegle marmelos), Podophyllotoxin (Podophyllum hexandrum), and Plumbagin (Plumbago zeylanica), among others, are some important anticancer phytochemicals extracted from plant species found in the Himalayan region (Ashraf 2020). Table 3 lists the anticancer effects of some Himalayan plants.

Table 3 In vitro and in vivo anticancer effects of plants from the Himalayan region
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6.2 Neuroprotective Activity

Neurodegenerative diseases comprise an anomalous group of disorders that are described by continuous declining or worsening of the peripheral nervous system or CNS structure and function. These neurodegenerative diseases are basically age dependent (Heemels 2016), with Alzheimer’s disease (AD) and Parkinson's disease (PD) being the most common, despite Huntington's disease (HD), amyotrophic lateral sclerosis (ALS), spinocerebellar ataxias, and frontotemporal dementia being increasingly diagnosed.

AD is a progressive and irreversible brain disorder that gradually damages the memory and thinking skills and eventually results in inability to perform simple tasks. PD is characterized by a continuous loss of dopamine resulting in movement disorder, rigidity, and tremor, as well as neuron demise in cholinergic and catecholaminergic nuclei. Sparreboom et al. (2004) reported that a huge population of Australia, Europe, and North America are using plant-derived medicines for treating such conditions. Although many modern medicines are available in the market for neurodegenerative diseases, plant-based drugs have also left their promising impression in this field. In fact, among the Himalayan flora, Artemisia absinthium, Bergenia ciliate, Centella asiatica, Crocus sativus, Curcuma longa, Elaeagnus umbellata, Lindera neesiana, Myrica esculenta, Panax ginseng, Swertia chirayita, Valeriana officinalis, and W. somnifera are some examples of plants with remarkable neuroprotective abilities (Table 4).

Table 4 Bioactive compounds with neuroprotective effects
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6.3 Antidiabetic Activity

Diabetes is a chronic metabolic disease with a huge public health impact (Modak et al. 2007; Osadebe et al. 2014) that results from either insulin dysfunction or insulin deficiency in the body. Currently, there are three major types of diabetes, type I, type II, and gestational diabetes, which are responsible for sickness and premature fatality rate (Cade 2008). Indeed, diabetes is considered as a fifth leading cause of death in the twenty-first century, and as per data, more than 2.8% of the world’s population is suffering from diabetes, and it is expected that the number of cases will raise to more than 5.4% by 2025 (Mukesh and Namita 2013; Kazi 2014). Pharmacotherapy, diet therapy, and insulin therapy are the most common modern therapeutic strategies for such conditions. Although modern treatments are available, complete treatment and prevention of diabetes still seem impossible due to some disadvantages, including side effects, drug resistance, and even drug-related toxicity (Kooti et al. 2016). Therefore, plant-based drugs have been highly recommended for the treatment of such affections (Kooti et al. 2015). Phytochemicals, like flavonoids, alkaloids, terpenoids, and glycosides , have shown interesting antidiabetic effects (Afrisham et al. 2015), with some Himalayan plants revealing an interesting potential (Table 5).

Table 5 Himalayan plant species with antidiabetic potential
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6.4 Antimicrobial Activity

Worldwide, the burden of infectious diseases is increasing at a frightening rate, causing death in millions (Bhutta et al. 2014). To fight such infectious diseases, many modern medicines have become available in the market, but along with their therapeutic activity, severe side effects have also been reported. In addition, currently, an increasing amount of multidrug-resistant microorganisms (MDRM) have become a key matter of concern. Therefore, it becomes an urgent and important need to develop powerful and safe drugs against microbial diseases at the right time.

Worldwide, many research groups are showing greater interest in developing antimicrobial drugs from plant source as they are more effective against microbial infections and have been safer for both humans and the environment, along with that where existing antibiotics showed no or less activity against multidrug resistance microorganisms (MDRM), plant-based drugs naturally boost immunity and show promising activity against MDRM (Subramani et al. 2017). A wide range of phytoconstituents, such as phenols, flavonoids, tannins, quinine, and coumarins, have been reported with significant antimicrobial activities (Cushnie and Lamb 2005; Kurhekar 2016; Cueva et al. 2010; Al-Majedy et al. 2017; Scalbert 1991; Antika et al. 2020). Moreover, from a long back, the Himalayan region communities have been using native plant species to treat different microbial diseases from which some important species are mentioned in Table 6.

Table 6 Antioxidant and antimicrobial studies in different Himalayan regions
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6.5 Antioxidant Activity

Recently, more interest has arisen toward natural antioxidants and their role in human health maintenance and disease prevention. Briefly, in healthy individuals, antioxidants regulate the homeostasis between free radicals’ production and scavenging; however, antioxidants depletion results in higher production of free radicals triggering oxidative stress, which ultimately leads to several disturbances in the whole organism. As a matter of fact, oxidative stress is responsible for oxidation at both cell and molecular levels and further leads to cells/tissues damage being associated with a plethora of diseases, like neurodegenerative, metabolic, osteoarticular, cardiovascular and immune system disorders, and even cancer (Jonah 2013).

The Himalayan medicinal plants are highly acknowledged for their nutritional phytoconstituents and antioxidant effects. Indeed, phytoconstituents, like flavonoids, lignans, catechins, phenols, coumarins, isocatechins, isoflavones, and anthocyanins, have been widely recognized for their antioxidant properties (Prior 2003; Cai et al. 2004).

The determination of the antioxidant potential of plants, its derived extracts, and even isolated constituents can be analyzed by different in vitro (2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid [ABTS], 2,2-diphenyl-1-picrylhydrazyl [DPPH], oxygen radical absorbance capacity (ORAC), thiobarbituric acid reactive substances [TBARS], ferric reducing antioxidant power [FRAP] and Trolox equivalent antioxidant capacity [TEAC] assays) and in vivo methods, with a series of medicinal plants already been studied by different research groups around the world. As some examples, the crude methanol extracts from Bunium persicum (seeds), Dactylorhiza hatageria (tubers), Satyrium nepalense (tubers), Viscum album (fruits), and Urtica dioica (leaves) have revealed interesting antioxidant effects by the DPPH assay, with IC50 values of 0.09, 0.21, 0.04, 0.42, and 0.14 mg/mL, respectively (Kawra et al. 2020). Also, the methanol extracts from Trillium govanianum rhizome, leaf, and stem showed maximum DPPH, ABTS, and FRAP activities with 16.06 milli molar ascorbic acid extract/gram fresh weight (mM AAE/g fw), 4.39 mM AAE/g fw, and 2.17 mM AAE/g fw, respectively (Kundra et al. 2020). Moreover, Painuli et al. (2018) reported antioxidant effects of Rhododendron arboreum and Rhododendron campanulatum leaves aqueous and methanol extract by DPPH, FRAP, ABTS, and total reducing power assay. Saussurea obvallata leaves and flowers methanol and water extracts also displayed DPPH and H2O2 free radical scavenging activities (Semwal and Painuli 2019). Other plant extracts, such as Acorus calmus (rhizome), Habenaria intermedia (tuber), Hedychium spicatum (rhizome), Roscoea procera (rhizome), and Valeriana jatamansi (root), also revealed interesting antioxidant effects through DPPH, ABTS, and FRAP assays (Rawat et al. 2017). Few other antioxidant-rich Himalayan plant species are listed in Table 6.

7 Conclusion and Upcoming Perspectives

The Himalayan region is famous worldwide for its unique, diverse, valuable, and endemic flora and fauna. Several highly valuable medicinal plants have been documented from this region, and these plants play a notable role in the human health care system. Many research groups have been increasingly devoted to the study of the therapeutic applications of a plethora of plants as well as on phytoconstituents’ identification and related mechanism of action. However, despite the advance stated so far, many phytochemicals remain to be identified, and the mechanism of action of many others against various diseases is still unclear; therefore, much research is needed in this regard. On the other hand, medicinal plants in the Himalayan region face erratic harvests due to the growing demand for essential oils, herbal preparations, and drug formulation due to which many important plants have been extinct and many are on the verge of extinction. Thus, exploring more data on such plant species and their respective properties is an important issue, while protection and sustainable conservation too.